Type IV hypersensitivity

Melamed J, Beaucher WN Delayed-type hypersensitivity (type IV) reactions in dental anesthesia. Allergy Asthma Proc 2007 28 477-479. 

Occupational exposure to beryllium, a hapten, by inhalation of fumes/dust and/or by skin contact may result in one of two conditions that primarily affect the lungs. In acute berylliosis, which may occur following a high concentration exposure, the metal acts as a direct chemical irritant, causing a nonspecific inflammatory reaction (acute chemical pneumonitis). However, a small percentage of those exposed develop beryllium-specific T-cell-mediated hypersensitivity (Type IV) with proliferation and accu-... 

Immunologic Both immediate, type I reactions and delayed hypersensitivity, type IV reactions to systemic CS preparations have been reported. Type I reactions are rare, with delayed hypersensitivity reactions being slightly more common. Two case reports of immediate and delayed hypersensitivity to systemic CS have been published [40 ]. A 33-year-old woman with asthma attacks developed pruritus and hives 30 min after administration of parenteral CS, her respiratory status deteriorated after 6h, and an acute eczematous dermatitis developed on her face, neck and upper body after 24 h. A type I anaphylactoid reaction was diagnosed. A 51-year-old woman who developed urticarial lesions lasting about 30 min after injection of intralesional triamcinolone injections for keloid scars was diagnosed with type I allergy. 

Type IV allergic reactions are cell-mediated hypersensitivity reactions which are characterized by the expansion of T lymphocytes specific for foreign substances exposed on cell surfaces. In type FVa allergic reactions, this results in the cell-mediated destruction of the cells, whereas in type FVb allergic reactions an... 

Type IV reactions are mediated by T cells themselves. Delayed-type hypersensitivity reactions from positive tuberculin tests to contact dermatitis are typical type IV reactions, but understanding T-cell function allows us to further define this category, as shown in Table 51-1. 

It is believed that nickel penetrates the skin and acts as a hapten, complexing with selected peptide and/or amino-acid ligands to distort intercellular or cellular proteins, stimulating a type IV delayed (cell-mediated) hypersensitivity reaction [398]. Nickel water-soluble salts, like nickel chloride and nickel sulphate, are strong sensitizers [213, 215], The chloride induced in sweat is apparently an important factor in dissolving the metallic nickel, permitting the soluble nickel salts to act. 

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

Type IV Hypersensitivity. There are several well-established preclinical models for assessing Type IV (delayed-type) hypersensitivity reactions following dermal exposure, but not for predicting this response after systemic exposure. 

Type IV hypersensitivity responses are elicited by T lymphocytes and are controlled by accessory cells and suppressor T cells. Macrophages are also involved in that they secrete several monokines, which results in proliferation and differentiation of T cells. Thus, there are numerous points along this intricate pathway in which drugs may modulate the final response. To achieve a Type IV response, an initial high-dose exposure or repeated lower-dose exposures are applied to the skin the antigen is carried from the skin by Langerhans cells and presented to cells in the thymus to initiate T-cell proliferation and sensitization. Once sensitized, a second challenge dose will elicit an inflammatory response. Thus, before sensitivity can be assessed, each of the models used to evaluate dermal hypersensitivity requires as a minimum ... 

Toxicology. NRL causes allergic skin reactions of type I (immediate-type) and type IV [delayed-type hypersensitivity (DTH)]. 

Toxicology. Zinc dithiocarbamates (ZDC) are contact allergens and are one of the chemical groups in rubber that cause the type IV delayed-type hypersensitivity skin reaction (DTH). ... 

There is also a possibility that someone can develop a type IV delayed hypersensitivity to some monomers. Of the monomers used, TEGDMA and HEMA may have the highest incident of sensitivity, but that incidence is extremely low. Though there are no literature reports of toxicity to composite resins over the 30 years of dental use, there are investigations into the potential for at least an allergic response to degradation products or extractable components [181]. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

Hypersensitivity can be classified as antibody-mediated or cell-mediated. Three types of hypersensitivity are antibody-mediated (types I—III), while the fourth is cell-mediated (type IV). Hypersensitivity occurs in two phases the sensitization phase and the effector phase. Sensitization occurs upon initial encounter with an antigen the effector phase involves immunologic memory and results in tissue pathology upon a subsequent encounter with that antigen. 

Figure 6.34 The basis of type IV hypersensitivity reactions. This is cell mediated rather than antibody mediated.

Type IV hypersensitivity reactions. This type of immune response is unlike the other three in that antibodies are not involved, the response being initiated by sensitized ThI cells. 

Type IV Reactions Also termed delay-type hypersensitivity reaction, these take 48-72 h to develop and are not antibody-mediated. Antigens are recognized by CD4+ and/or CD8+ cells in the context of MHC class restrictions on APCs. These reactions are T-cell-mediated where activated T cells release cytokines, resulting in the development of granulomas from macrophages. These mechanisms are responsible for symptoms that may include transplant rejection, contact dermatitis, leprosy, tuberculosis and sarcoidosis. 

A 45-year-old woman who had used insulin for 4 years had a biphasic hypersensitivity reaction to human insulin (or another component of the injection fluid) (135). Within 20 minutes after the injection a swelling developed and in a later phase papular lesions with lichenoid features and post-inflammatory hyperpigmentation emerged. Histologically, there was neutrophilic infiltration with erythrocyte extravasation and eosinophilic amorphous material, surrounded by neutrophilic infiltrate. Saline injection did not elicit an effect. IgE anti-insulin antibodies were not found. There was no Arthus reaction (type IV allergy). 

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